The stiffness primarily affects the truncal muscles and is characterised by spasms, resulting in postural deformities.

[2] Stiff-person syndrome (SPS) is often separated into several subtypes, based on the cause and progression of the disease.

[6] Eventually, rigidified muscles reduce the affected person's range of motion, slow their voluntary movements, and may cause them to have abnormal posture, particularly lumbar hyperlordosis (a distinctive curve in the lower back).

[6] Rigid trunk muscles can also prevent the chest and abdomen from expanding, causing shortness of breath and early satiety.

[6] Alongside growing stiffness, many with SPS develop bouts of muscle spasms that are triggered by sudden movements and feeling upset or startled.

[6] Spasms are sometimes accompanied by elevated blood pressure, heart rate, body temperature, and sweating.

[6] The muscle stiffness initially fluctuates, sometimes for days or weeks, but eventually begins to consistently impair mobility.

Attacks of spasms are unpredictable and are often caused by fast movements, emotional distress, or sudden sounds or touches.

[8] In rare cases, facial muscles, hands, feet, and the chest can be affected, and unusual eye movements and vertigo occur.

[18] Around 5% of those with SPS experience the symptoms as a paraneoplastic syndrome — a result of a tumor elsewhere in the body releasing bioactive molecules.

[19][20] Patients with SPS generally have high glutamic acid decarboxylase (GAD) antibody levels in their blood.

[23] GAD, a presynaptic autoantigen, is generally thought to play a key role in the condition, but exact details of the way autoantibodies affect SPS patients are not known.

[24] The antibodies appear to interact with antigens in the brain neurons and the spinal-cord synapses, causing a functional blockade of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).

[7] The excessive firing of motor neurons may be caused by malfunctions in spinal and suprasegmental inhibitory networks that use GABA.

[7] Involuntary actions show up as voluntary on EMG scans;[13] even when the patient tries to relax, agonist and antagonist contractions occur.

[22] In a minority of patients with SPS, breast, ovarian, or lung cancer manifests paraneoplastically as proximal muscle stiffness.

[5] Due to the rarity and varied symptoms of SPS, most affected by the disease wait several years before they are correctly diagnosed.

[5] The presence of antibodies against GAD is the best indication of the condition that can be detected by blood and cerebrospinal fluid (CSF) testing.

[7] It can confirm the SPS diagnosis by noting spasms in distant muscles as a result of subnoxious stimulation of cutaneous or mixed nerves.

[13] Responsiveness to diazepam helps confirm that the patient has SPS, as this drug decreases stiffness and motor-unit firing.

[7] CT scans are indicated for SPS patients who respond poorly to therapy to determine if cancer is the cause.

[30] A variety of conditions have similar symptoms to SPS, including myelopathies, dystonias, spinocerebellar degenerations, primary lateral sclerosis, neuromyotonia, and some psychogenic disorders.

[31] Nonetheless, first line treatment strategies include managing the symptoms with GABA-ergic drugs, such as diazepam and baclofen.

They observed "persistent tonic contraction reflected in constant firing, even at rest" after providing patients with muscle relaxants and examining them with electromyography.

[42] In 1993, antiamphiphysin was shown to play a role in paraneoplastic SPS,[24] and seven years later, antigephyrin was also found to be involved in the condition.

[24] In December 2022, singer Céline Dion announced that she is suffering from this syndrome, resulting in cancelled performances.